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  • Incorporating dixon multi-echo fat water separation for novel quantitative magnetization transfer of the human optic nerve in vivo.

    20 March 2018

    PURPOSE: The optic nerve (ON) represents the sole pathway between the eyes and brain; consequently, diseases of the ON can have dramatic effects on vision. However, quantitative magnetization transfer (qMT) applications in the ON have been limited to ex vivo studies, in part because of the fatty connective tissue that surrounds the ON, confounding the magnetization transfer (MT) experiment. Therefore, the aim of this study was to implement a multi-echo Dixon fat-water separation approach to remove the fat component from MT images. METHODS: MT measurements were taken in a single slice of the ON and frontal lobe using a three-echo Dixon readout, and the water and out-of-phase images were applied to a two-pool model in ON tissue and brain white matter to evaluate the effectiveness of using Dixon fat-water separation to remove fatty tissue from MT images. RESULTS: White matter data showed no significant differences between image types; however, there was a significant increase (p < 0.05) in variation in the out-of-phase images in the ON relative to the water images. CONCLUSIONS: The results of this study demonstrate that Dixon fat-water separation can be robustly used for accurate MT quantification of anatomies susceptible to partial volume effects resulting from fat. Magn Reson Med 77:707-716, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

  • Short Term Reproducibility of a High Contrast 3-D Isotropic Optic Nerve Imaging Sequence in Healthy Controls.

    9 May 2018

    The optic nerve (ON) plays a crucial role in human vision transporting all visual information from the retina to the brain for higher order processing. There are many diseases that affect the ON structure such as optic neuritis, anterior ischemic optic neuropathy and multiple sclerosis. Because the ON is the sole pathway for visual information from the retina to areas of higher level processing, measures of ON damage have been shown to correlate well with visual deficits. Increased intracranial pressure has been shown to correlate with the size of the cerebrospinal fluid (CSF) surrounding the ON. These measures are generally taken at an arbitrary point along the nerve and do not account for changes along the length of the ON. We propose a high contrast and high-resolution 3-D acquired isotropic imaging sequence optimized for ON imaging. We have acquired scan-rescan data using the optimized sequence and a current standard of care protocol for 10 subjects. We show that this sequence has superior contrast-to-noise ratio to the current standard of care while achieving a factor of 11 higher resolution. We apply a previously published automatic pipeline to segment the ON and CSF sheath and measure the size of each individually. We show that these measures of ON size have lower short-term reproducibility than the population variance and the variability along the length of the nerve. We find that the proposed imaging protocol is (1) useful in detecting population differences and local changes and (2) a promising tool for investigating biomarkers related to structural changes of the ON.

  • Contrast mechanisms associated with neuromelanin-MRI.

    14 May 2018

    PURPOSE: To investigate the physical mechanisms associated with the contrast observed in neuromelanin MRI. METHODS: Phantoms having different concentrations of synthetic melanins with different degrees of iron loading were examined on a 3 Tesla scanner using relaxometry and quantitative magnetization transfer (MT). RESULTS: Concentration-dependent T1 and T2 shortening was most pronounced for the melanin pigment when combined with iron. Metal-free melanin had a negligible effect on the magnetization transfer spectra. On the contrary, the presence of iron-laden melanins resulted in a decreased magnetization transfer ratio. The presence of melanin or iron (or both) did not have a significant effect on the macromolecular content, represented by the pool size ratio. CONCLUSION: The primary mechanism underlying contrast in neuromelanin-MRI appears to be the T1 reduction associated with melanin-iron complexes. The macromolecular content is not significantly influenced by the presence of melanin with or without iron, and thus the MT is not directly affected. However, as T1 plays a role in determining the MT-weighted signal, the magnetization transfer ratio is reduced in the presence of melanin-iron complexes. Magn Reson Med 78:1790-1800, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

  • Rapid, high-resolution quantitative magnetization transfer MRI of the human spinal cord.

    30 April 2018

    Quantitative magnetization transfer (qMT) imaging can provide indices describing the interactions between free water protons and immobile macromolecular protons. These indices include the macromolecular proton fraction (MPF), which has been shown to correlate with myelin content in white matter. Because of the long scan times required for high-resolution spinal cord imaging, qMT studies of the human spinal cord have not found wide-spread application. Herein, we investigated whether these limitations could be overcome by utilizing only a single MT-weighted acquisition and a reference measurement, as was recently proposed in the brain. High-resolution, in vivo qMT data were obtained at 3.0T in the spinal cords of healthy volunteers and patients with relapsing remitting multiple sclerosis (MS). Low- and high-resolution acquisitions (low/high resolution=1×1×5mm(3)/0.65×0.65×5mm(3)) with clinically acceptable scan times (12min/7min) were evaluated. We also evaluated the reliability over time and the sensitivity of the model to the assumptions made in the single-point method, both in disease and healthy tissues. Our findings suggest that the single point qMT technique can provide maps of the MPF in the spinal cord in vivo with excellent grey/white matter contrast, can be reliably obtained within reasonable scan times, and are sensitive to MS pathology. Consistent with previous qMT studies in the brain, the observed MPF values were higher in healthy white matter (0.16±0.01) than in grey matter (0.13±0.01) and in MS lesions (0.09±0.01). The single point qMT technique applied at high resolution provides an improved method for obtaining qMT in the human spinal cord and may offer a reliable outcome measure for evaluating spinal cord disease.

  • Amide proton transfer CEST of the cervical spinal cord in multiple sclerosis patients at 3T.

    26 April 2018

    PURPOSE: The ability to evaluate pathological changes in the spinal cord in multiple sclerosis (MS) is limited because T1 - and T2 -w MRI imaging are not sensitive to biochemical changes in vivo. Amide proton transfer (APT) chemical exchange saturation transfer (CEST) can indirectly detect amide protons associated with proteins and peptides, potentially providing more pathological specificity. Here, we implement APT CEST in the cervical spinal cord of healthy and MS cohorts at 3T. METHODS: APT CEST of the cervical spinal cord was obtained in a cohort of 10 controls and 10 MS patients using a novel respiratory correction methodology. APT was quantified using two methods: 1) APTw , based off the conventional magnetization transfer ratio asymmetry, and 2) ΔAPT, a spatial characterization of APT changes in MS patients relative to the controls. RESULTS: Respiratory correction yielded highly reproducible z-spectra in white matter (intraclass correlation coefficient = 0.82). APTw signals in normal-appearing white matter (NAWM) of MS patients were significantly different from healthy controls (P = 0.04), whereas ΔAPT of MS patients highlighted large APT differences in NAWM. CONCLUSION: Respiration correction in the spinal cord is necessary to accurately quantify APT CEST, which can provide unique biochemical information regarding disease processes within the spinal cord. Magn Reson Med 79:806-814, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

  • Improved Automatic Optic Nerve Radius Estimation from High Resolution MRI.

    9 May 2018

    The optic nerve (ON) is a vital structure in the human visual system and transports all visual information from the retina to the cortex for higher order processing. Due to the lack of redundancy in the visual pathway, measures of ON damage have been shown to correlate well with visual deficits. These measures are typically taken at an arbitrary anatomically defined point along the nerve and do not characterize changes along the length of the ON. We propose a fully automated, three-dimensionally consistent technique building upon a previous independent slice-wise technique to estimate the radius of the ON and surrounding cerebrospinal fluid (CSF) on high-resolution heavily T2-weighted isotropic MRI. We show that by constraining results to be three-dimensionally consistent this technique produces more anatomically viable results. We compare this technique with the previously published slice-wise technique using a short-term reproducibility data set, 10 subjects, follow-up <1 month, and show that the new method is more reproducible in the center of the ON. The center of the ON contains the most accurate imaging because it lacks confounders such as motion and frontal lobe interference. Long-term reproducibility, 5 subjects, follow-up of approximately 11 months, is also investigated with this new technique and shown to be similar to short-term reproducibility, indicating that the ON does not change substantially within 11 months. The increased accuracy of this new technique provides increased power when searching for anatomical changes in ON size amongst patient populations.

  • Self-Management Support Using a Digital Health System Compared With Usual Care for Chronic Obstructive Pulmonary Disease: Randomized Controlled Trial.

    21 May 2018

    BACKGROUND: We conducted a randomized controlled trial of a digital health system supporting clinical care through monitoring and self-management support in community-based patients with moderate to very severe chronic obstructive pulmonary disease (COPD). OBJECTIVE: The aim of this study was to determine the efficacy of a fully automated Internet-linked, tablet computer-based system of monitoring and self-management support (EDGE' sElf-management anD support proGrammE) in improving quality of life and clinical outcomes. METHODS: We compared daily use of EDGE with usual care for 12 months. The primary outcome was COPD-specific health status measured with the St George's Respiratory Questionnaire for COPD (SGRQ-C). RESULTS: A total of 166 patients were randomized (110 EDGE, 56 usual care). All patients were included in an intention to treat analysis. The estimated difference in SGRQ-C at 12 months (EDGE-usual care) was -1.7 with a 95% CI of -6.6 to 3.2 (P=.49). The relative risk of hospital admission for EDGE was 0.83 (0.56-1.24, P=.37) compared with usual care. Generic health status (EQ-5D, EuroQol 5-Dimension Questionnaire) between the groups differed significantly with better health status for the EDGE group (0.076, 95% CI 0.008-0.14, P=.03). The median number of visits to general practitioners for EDGE versus usual care were 4 versus 5.5 (P=.06) and to practice nurses were 1.5 versus 2.5 (P=.03), respectively. CONCLUSIONS: The EDGE clinical trial does not provide evidence for an effect on COPD-specific health status in comparison with usual care, despite uptake of the intervention. However, there appears to be an overall benefit in generic health status; and the effect sizes for improved depression score, reductions in hospital admissions, and general practice visits warrants further evaluation and could make an important contribution to supporting people with COPD. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 40367841; (Archived by WebCite at

  • Does cognitive behavioural therapy for insomnia improve cognitive performance? A systematic review and narrative synthesis.

    21 May 2018

    Individuals with insomnia report difficulties pertaining to their cognitive functioning. Cognitive behavioural therapy for insomnia (CBT-I) is associated with robust, long-term improvements in sleep parameters, however less is known about the impact of CBT-I on the daytime correlates of the disorder. A systematic review and narrative synthesis was conducted in order to summarise and evaluate the evidence regarding the impact of CBT-I on cognitive functioning. Reference databases were searched and studies were included if they assessed cognitive performance as an outcome of CBT-I, using either self-report questionnaires or cognitive tests. Eighteen studies met inclusion criteria, comprising 923 individuals with insomnia symptoms. The standardised mean difference was calculated at post-intervention and follow-up. We found preliminary evidence for small to moderate effects of CBT-I on subjective measures of cognitive functioning. Few of the effects were statistically significant, likely due to small sample sizes and limited statistical power. There is a lack of evidence with regards to the impact of CBT-I on objective cognitive performance, primarily due to the small number of studies that administered an objective measure (n = 4). We conclude that adequately powered randomised controlled trials, utilising both subjective and objective measures of cognitive functioning are required.

  • Oscillatory neural representations in the sensory thalamus predict neuropathic pain relief by deep brain stimulation.

    17 May 2018

    OBJECTIVE: Understanding the function of sensory thalamic neural activity is essential for developing and improving interventions for neuropathic pain. However, there is a lack of investigation of the relationship between sensory thalamic oscillations and pain relief in patients with neuropathic pain. This study aims to identify the oscillatory neural characteristics correlated with pain relief induced by deep brain stimulation (DBS), and develop a quantitative model to predict pain relief by integrating characteristic measures of the neural oscillations. APPROACH: Measures of sensory thalamic local field potentials (LFPs) in thirteen patients with neuropathic pain were screened in three dimensional feature space according to the rhythm, balancing, and coupling neural behaviours, and correlated with pain relief. An integrated approach based on principal component analysis (PCA) and multiple regression analysis is proposed to integrate the multiple measures and provide a predictive model. MAIN RESULTS: This study reveals distinct thalamic rhythms of theta, alpha, high beta and high gamma oscillations correlating with pain relief. The balancing and coupling measures between these neural oscillations were also significantly correlated with pain relief. SIGNIFICANCE: The study enriches the series research on the function of thalamic neural oscillations in neuropathic pain and relief, and provides a quantitative approach for predicting pain relief by DBS using thalamic neural oscillations.